Various Cancer Types

EAY191-E4



Testing the Use of Nilotinib and Paclitaxel as a Treatment for Patients with Prior Taxane Treatment, A ComboMATCH Treatment Trial

STATUS: Active


This phase II ComboMATCH treatment trial evaluates nilotinib with paclitaxel for the treatment of patients with solid cancers that are growing, spreading, or getting worse (progressive) and that have previously been treated with taxane therapies. Nilotinib is in a class of medications called kinase inhibitors. It works by binding to and blocking the action of a protein called ABL, which signals tumor cells to multiply. This helps slow or stop the proliferation of tumor cells. Paclitaxel is a drug that blocks cell growth by stopping cell division and it may kill tumor cells. Giving nilotinib with paclitaxel may be effective at treating patients with progressive solid cancers that have previously been treated with taxane therapies.
  • Patient must be enrolled on the ComboMATCH registration protocol (EAY191) at the time of registration to the EAY191-E4 study

  • Patient must be >= 18 years of age

  • Patient must not have any of the following mutations (as determined by the ComboMATCH registration protocol), which are known to confer sensitivity or resistance to nilotinib monotherapy: * KIT: W557R, V559D, V559A, L576P, and K642E * PDGFR-alpha: D842V

  • Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH registration trial (EAY191) * NOTE: The current actionable mutation of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website * NOTE: Novel/dynamic aMOI can be submitted for review per the process described in the ComboMATCH registration protocol

  • Patient must be willing to provide blood samples for research purposes

  • Patient must have had at least one prior line of therapy in the metastatic setting

  • Patient must have previously undergone taxane therapy (in the metastatic setting) * Patients who previously responded to prior taxane therapy must have received their last dose of taxane therapy within 6 months prior to EAY191-E4 registration and have had no other intervening treatment prior to EAY191-E4 registration * Patients who did not respond to prior taxane therapy are eligible regardless of the time elapsed since the prior taxane therapy or any other intervening therapies

  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

  • Patient must not have had platinum-resistant epithelial serous ovarian cancer

  • Patient must not have peripheral neuropathy > grade 1

  • Patients must not have neuropathy >= grade 2 within 14 days of registration/randomization

  • Patient must have documented QT interval with Fridericiaโ€™s correction (QTcF) of =< 450 msec within 8 days prior to EAY191-E4 registration. Patients with a QTcF interval of >= 450 msec at registration or patients with congenital long QT syndrome are not eligible

  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used * All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy * A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

  • Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 3 months after the last dose of study drug

  • Patients must have progressive disease

  • Absolute neutrophil count (ANC) >= 1,500/mcL

  • Platelets >= 100,000/mcL

  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (with the exception of those with Gilbert syndrome, who must have total bilirubin =< 3 x institutional ULN)

  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 institutional upper limit of normal; < 5.0 x ULN in patients with liver metastases

  • Creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 mg/dL

  • Patient must have the ability to swallow medications

United States
AL
Birmingham
University of Alabama at Birmingham Cancer Center
Contact: Site Public Contact
Email: tmyrick@uab.edu

CA
Palo Alto
Stanford Cancer Institute Palo Alto
Contact: Site Public Contact
Email: ccto-office@stanford.edu

Whittier
Presbyterian Intercommunity Hospital
Contact: Site Public Contact

IL
Bloomington
Illinois CancerCare-Bloomington
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Canton
Illinois CancerCare-Canton
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Carthage
Illinois CancerCare-Carthage
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Centralia
Centralia Oncology Clinic
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Chicago
John H Stroger Jr Hospital of Cook County
Contact: Site Public Contact

Danville
Carle at The Riverfront
Contact: Site Public Contact
Email: Research@Carle.com

Decatur
Cancer Care Specialists of Illinois - Decatur
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Decatur Memorial Hospital
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Dixon
Illinois CancerCare-Dixon
Contact: Site Public Contact

Effingham
Carle Physician Group-Effingham
Contact: Site Public Contact
Email: Research@carle.com

Crossroads Cancer Center
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Eureka
Illinois CancerCare-Eureka
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Galesburg
Illinois CancerCare-Galesburg
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Kewanee
Illinois CancerCare-Kewanee Clinic
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Macomb
Illinois CancerCare-Macomb
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Mattoon
Carle Physician Group-Mattoon/Charleston
Contact: Site Public Contact
Email: Research@carle.com

Ottawa
Illinois CancerCare-Ottawa Clinic
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Pekin
Illinois CancerCare-Pekin
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Peoria
Illinois CancerCare-Peoria
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Peru
Illinois CancerCare-Peru
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Princeton
Illinois CancerCare-Princeton
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

Springfield
Memorial Medical Center
Contact: Site Public Contact
Email: pallante.beth@mhsil.com

Southern Illinois University School of Medicine
Contact: Site Public Contact

Springfield Clinic
Contact: Site Public Contact

Urbana
Carle Cancer Center
Contact: Site Public Contact
Email: Research@carle.com

Washington
Illinois CancerCare - Washington
Contact: Site Public Contact
Email: andersonj@illinoiscancercare.com

KY
Lexington
University of Kentucky/Markey Cancer Center
Contact: Site Public Contact

LA
New Orleans
Ochsner Medical Center Jefferson
Contact: Site Public Contact
Email: Elisemarie.curry@ochsner.org

MD
Bethesda
National Institutes of Health Clinical Center
Contact: Site Public Contact

MI
Ann Arbor
Saint Joseph Mercy Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Brighton
Saint Joseph Mercy Brighton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Brighton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Canton
Saint Joseph Mercy Canton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Canton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Chelsea
Saint Joseph Mercy Chelsea
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Flint
Genesee Cancer and Blood Disease Treatment Center
Contact: Site Public Contact
Email: wstrong@ghci.org

Genesee Hematology Oncology PC
Contact: Site Public Contact
Email: wstrong@ghci.org

Genesys Hurley Cancer Institute
Contact: Site Public Contact
Email: wstrong@ghci.org

Hurley Medical Center
Contact: Site Public Contact
Email: wstrong@ghci.org

Lansing
Sparrow Hospital
Contact: Site Public Contact

Livonia
Trinity Health Saint Mary Mercy Livonia Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Ypsilanti
Huron Gastroenterology PC
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

MO
Cape Girardeau
Saint Francis Medical Center
Contact: Site Public Contact
Email: sfmc@sfmc.net

Farmington
Parkland Health Center - Farmington
Contact: Site Public Contact

Saint Louis
Missouri Baptist Medical Center
Contact: Site Public Contact

Sainte Genevieve
Sainte Genevieve County Memorial Hospital
Contact: Site Public Contact

Sullivan
Missouri Baptist Sullivan Hospital
Contact: Site Public Contact

Sunset Hills
Missouri Baptist Outpatient Center-Sunset Hills
Contact: Site Public Contact

NV
Henderson
OptumCare Cancer Care at Seven Hills
Contact: Site Public Contact
Email: research@sncrf.org

Las Vegas
OptumCare Cancer Care at Charleston
Contact: Site Public Contact
Email: research@sncrf.org

NY
Buffalo
Roswell Park Cancer Institute
Contact: Site Public Contact
Email: askroswell@roswellpark.org

OH
Dayton
Dayton Physician LLC-Miami Valley Hospital North
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Kettering
Kettering Medical Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Toledo
Toledo Clinic Cancer Centers-Toledo
Contact: Site Public Contact

OK
Oklahoma City
University of Oklahoma Health Sciences Center
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

TX
Houston
M D Anderson Cancer Center
Contact: Site Public Contact
Email: askmdanderson@mdanderson.org

WI
Madison
University of Wisconsin Carbone Cancer Center
Contact: Site Public Contact

PRIMARY OBJECTIVE:
I. To evaluate the proportion of patients with taxane-refractory advanced malignancies who have objective responses (OR) to treatment with nilotinib hydrochloride monohydrate (nilotinib) and paclitaxel.

SECONDARY OBJECTIVE:
I. Collect tissue and provide it to the ComboMATCH registration protocol to assess concordance between the diagnostic tumor mutation profile generated by the designated laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) mutation profile from plasma, as described in ComboMATCH registration protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH registration protocol.

EXPLORATORY OBJECTIVES:
I. To evaluate progression free survival (PFS) at 6 months on study agents.
II. To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens and cell-free deoxyribonucleic acid (DNA).

OUTLINE:
Patients receive nilotinib hydrochloride monohydrate orally (PO) twice daily (BID) on days 1-28 and paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Patients also undergo collection of blood samples and tumor biopsy on study.

After completion of study treatment, patients are followed until disease progression, and for survival for 3 years from registration.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network. This trial is part of the ComboMATCH precision medicine intiative.


EAY191-E4 / ComboMATCH Home Page
ECOG-ACRIN Cancer Research Group